The Endocrine Society has issued its first ever clinical practice guideline on the diagnosis and treatment of primary adrenal insufficiency — a life-threatening endocrine disorder characterized by the insufficient production of glucocorticoids and/or mineralocorticoids by the adrenal cortex.
Commonly known as Addison’s disease, primary adrenal insufficiency is rare, with a reported prevalence of 100 to 140 cases per million and an incidence of 4 cases per million annually in Western societies.
The guideline, published online and in the February 2016 print issue of the Journal of Clinical Endocrinology & Metabolism, was co-sponsored by the European Society of Endocrinology and the American Association for Clinical Chemistry.
The task force charged with creating the guideline based its recommendations on the best available evidence from existing studies and systematic reviews on primary adrenal insufficiency, as well as results from 2 systematic reviews. Both reviews were commissioned by the task force.
One review evaluated the accuracy of high-dose adrenocorticotropic hormone (ACTH) vs low-dose ACTH stimulation tests used in the initial diagnosis of primary adrenal insufficiency; the other assessed various glucocorticoid replacement regimens.
The guideline includes recommendations in 5 areas:
- Who should be treated and how;
- Optimal diagnostic tests;
- Treatment of primary adrenal insufficiency in adults;
- Management and prevention of adrenal crisis; and
- Monitoring requirements.
The treatment section is further broken out into sections covering glucocorticoid replacement; mineralocorticoid replacement; dehydroepiandrosterone (DHEA) replacement; treatment during pregnancy; and treatment and monitoring during childhood.
Diagnosis: Screening and Confirmation
Due to the rarity of Addison’s disease as well as its nonspecific symptoms, diagnostic delays are common, potentially leading to increased morbidity and mortality.
To prevent these delays, the guideline recommends that primary adrenal insufficiency be ruled out in all patients with indicative clinical symptoms or signs, especially acutely ill patients, patients with predisposing factors such as autoimmune disorders or relevant drugs, and pregnant women with unexplained persistent nausea, fatigue, and hypotension.
“[T]he current most pressing need for the treatment of primary adrenal insufficiency is the early diagnosis,” task force member Andreas Barthel, MD, of the Universitätsklinikum Dresden and Endokrinologikum Ruhr in Bochum, Germany, wrote in an email to Endocrinology Advisor. “In order to accomplish this, we need to increase our awareness for the disease and add primary adrenal insufficiency early to the list of differential diagnosis in severely ill patients with particular symptoms and signs like hypotension, hyponatremia, fever, abdominal pain, hyperpigmentation, or hypoglycemia.”
Christian Koch, MD, professor of medicine and director of endocrinology at the University of Mississippi Medical Center, noted that the diagnosis of primary adrenal insufficiency in the community is currently suboptimal.
“Many physicians, mostly non-endocrinologists, do not currently have a very high level of suspicion for primary adrenal insufficiency, as indicated by the lack of knowledge that secondary adrenal insufficiency can be caused by administering high-dose topical glucocorticoids, inhaled glucocorticoids, injecting dexamethasone for sinusitis, and other conditions that should not call for glucocorticoid treatment,” he explained. “Hypoglycemia often is overlooked as a possible presentation of primary adrenal insufficiency. Hyponatremia also is often not investigated further for existing primary adrenal insufficiency before making a diagnosis of SIADH (syndrome of inappropriate antidiuretic hormone).”
The diagnostic tests recommended in the guideline include determination of serum cortisol and plasma ACTH for screening and the corticotropin stimulation test as a confirmatory test.